Our objective is to provide aspects of the basic and applied research needed to lead to the development of safe, selective, biodegradable, and economically feasible insect control agents. For such compounds to be developed, we must understand comparative insect and mammalian biochemistry and xenobiotic metabolism, as well as the mechanism of nontarget effects of insecticides. Our specific aims are: I. The regulation and specificity of enzymes involved in insect juvenile hormone (JH) metabolism will be investigated and this informaton in the development of pest control agents exploited. This aim will be accomplished by studying JH esterases and epoxide hydrases. The mechanism of JH esterase regulation will be determined. Phosphoramidates and "transition state mimics" will be examined as inhibitors. Similar studies will be carried out with insect epoxide hydrases. II. The mechanism of action of anti-juvenile hormones will be explored by investigating the action of imidazole inhibitors of JH biosynthesis and by exploring the mechanism of action of JH agonist/antagonist molecules such as ETB. III. The soluble or cytoplasmic mammalian epoxide hydrase as a major route of xenobiotic metabolism will be investigated. Our substrate selectivity studies will be extended to epoxide-containing environmental contaminants and known mutagens. Substrate selectivity studies will be correlated with the ability of the soluble epoxide hydrase to protect Salmonella typhimurium from mutagenic epoxides in an Ames' assay. The kinetics of hydration of epoxides in the soluble and microsomal fraction of several mammalian species will be examined as work proceeds on the purification of the enzyme and the mechanism of hydration. IV. Specific problems with the development of new pest control agents will be solved as we develop an inexpensive residue analysis method for dienoate juvenoids and explore immunochemical technology for the analysis of benzoyl-phenylurea insect growth regulators.